Home LiteratureArticle Details
PMID: 21092857 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration.

Neuron ·Vol. 68 ·No. 4 ·2010-11-18 ·Pages 668-81

Kang SH, Fukaya M, Yang JK, Rothstein JD, Bergles DE

Abstract

The mammalian CNS contains a ubiquitous population of glial progenitors known as NG2+ cells that have the ability to develop into oligodendrocytes and undergo dramatic changes in response to injury and demyelination. Although it has been reported that NG2+ cells are multipotent, their fate in health and disease remains controversial. Here, we generated PDGFαR-CreER transgenic mice and followed their fate in vivo in the developing and adult CNS. These studies revealed that NG2+ cells in the postnatal CNS generate myelinating oligodendrocytes, but not astrocytes or neurons. In regions of neurodegeneration in the spinal cord of ALS mice, NG2+ cells exhibited enhanced proliferation and accelerated differentiation into oligodendrocytes but remained committed to the oligodendrocyte lineage. These results indicate that NG2+ cells in the normal CNS are oligodendrocyte precursors with restricted lineage potential and that cell loss and gliosis are not sufficient to alter the lineage potential of these progenitors.

MeSH Terms
Animals Animals, Newborn Cell Differentiation/genetics Cell Lineage/genetics Cell Proliferation Disease Models, Animal Mice Mice, Transgenic Nerve Degeneration/genetics,metabolism,pathology Neurogenesis/genetics Neuroglia/cytology,metabolism,ultrastructure Oligodendroglia/cytology,pathology,ultrastructure Random Allocation Receptor, Platelet-Derived Growth Factor alpha/genetics,physiology Spinal Cord/cytology,metabolism,ultrastructure Stem Cells/cytology,pathology,ultrastructure
Chemicals
Receptor, Platelet-Derived Growth Factor alpha
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kang Shin H
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
Fukaya Masahiro
Yang Jason K
Rothstein Jeffrey D
Bergles Dwight E
References (48)
48 references, click to expand
  1. Heterogeneity of NG2-expressing cells in the newborn mouse cerebellum.
    Dev Biol. 2005 Sep 15;285(2):409-21 PMID: 16084507
  2. PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice.
    Nat Neurosci. 2008 Dec;11(12):1392-401 PMID: 18849983
  3. Inducible site-specific recombination in myelinating cells.
    Genesis. 2003 Jan;35(1):63-72 PMID: 12481300
  4. Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke.
    Nat Med. 2008 Jul;14(7):731-7 PMID: 18568034
  5. Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter.
    Nat Neurosci. 2008 Apr;11(4):450-6 PMID: 18311136
  6. A global double-fluorescent Cre reporter mouse.
    Genesis. 2007 Sep;45(9):593-605 PMID: 17868096
  7. NG2 cells generate both oligodendrocytes and gray matter astrocytes.
    Development. 2008 Jan;135(1):145-57 PMID: 18045844
  8. Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond.
    J Cell Biol. 2009 Dec 14;187(6):761-72 PMID: 19951898
  9. CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination.
    Cell Stem Cell. 2010 Jun 4;6(6):578-90 PMID: 20569695
  10. The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury, in the brain.
    Neuroscience. 2004;127(4):813-20 PMID: 15312894
  11. Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord.
    J Neurosci. 2000 Mar 15;20(6):2218-28 PMID: 10704497
  12. Cell cycle dynamics of NG2 cells in the postnatal and ageing brain.
    Neuron Glia Biol. 2009 Nov;5(3-4):57-67 PMID: 20346197
  13. A noninvasive genetic/pharmacologic strategy for visualizing cell morphology and clonal relationships in the mouse.
    J Neurosci. 2003 Mar 15;23(6):2314-22 PMID: 12657690
  14. The oligodendrocyte-type-2 astrocyte cell lineage is specialized for myelination.
    Nature. 1986 Sep 25-Oct 1;323(6086):335-8 PMID: 3531873
  15. The basic helix-loop-helix factor olig2 is essential for the development of motoneuron and oligodendrocyte lineages.
    Curr Biol. 2002 Jul 9;12(13):1157-63 PMID: 12121626
  16. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons.
    J Cell Biol. 2003 Apr 14;161(1):169-86 PMID: 12682089
  17. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation.
    Science. 1994 Jun 17;264(5166):1772-5 PMID: 8209258
  18. Development of NG2 neural progenitor cells requires Olig gene function.
    Proc Natl Acad Sci U S A. 2006 May 16;103(20):7853-8 PMID: 16682644
  19. Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS.
    Glia. 1998 Jul;23(3):249-56 PMID: 9633809
  20. ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration.
    Nat Neurosci. 2008 Apr;11(4):420-2 PMID: 18344992
  21. Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity.
    Nat Rev Neurosci. 2009 Jan;10(1):9-22 PMID: 19096367
  22. NG2 cells generate oligodendrocytes and gray matter astrocytes in the spinal cord.
    Neuron Glia Biol. 2008 Feb;4(1):19-26 PMID: 19006598
  23. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells.
    Science. 2000 Sep 8;289(5485):1754-7 PMID: 10976069
  24. How widespread is adult neurogenesis in mammals?
    Nat Rev Neurosci. 2007 Jun;8(6):481-8 PMID: 17514200
  25. Inflammation in ALS and SMA: sorting out the good from the evil.
    Neurobiol Dis. 2010 Mar;37(3):493-502 PMID: 19833209
  26. Development and differentiation of glial precursor cells in the rat cerebellum.
    Glia. 1993 Apr;7(4):307-21 PMID: 8320001
  27. Response of the oligodendrocyte progenitor cell population (defined by NG2 labelling) to demyelination of the adult spinal cord.
    Glia. 1998 Feb;22(2):161-70 PMID: 9537836
  28. Myelination and the trophic support of long axons.
    Nat Rev Neurosci. 2010 Apr;11(4):275-83 PMID: 20216548
  29. Early postnatal proteolipid promoter-expressing progenitors produce multilineage cells in vivo.
    J Neurosci. 2009 Jun 3;29(22):7256-70 PMID: 19494148
  30. Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone.
    J Neurosci. 2004 Nov 17;24(46):10530-41 PMID: 15548668
  31. The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification.
    Cell. 2002 Apr 5;109(1):61-73 PMID: 11955447
  32. The oligodendrocyte precursor cell in health and disease.
    Trends Neurosci. 2001 Jan;24(1):39-47 PMID: 11163886
  33. Increased stem cell proliferation in the spinal cord of adult amyotrophic lateral sclerosis transgenic mice.
    J Neurochem. 2007 Aug;102(4):1125-38 PMID: 17472707
  34. Transient expression of the NG2 proteoglycan by a subpopulation of activated macrophages in an excitotoxic hippocampal lesion.
    Glia. 2001 Jun;34(4):296-310 PMID: 11360302
  35. Co-localization of NG2 proteoglycan and PDGF alpha-receptor on O2A progenitor cells in the developing rat brain.
    J Neurosci Res. 1996 Feb 01;43(3):299-314 PMID: 8714519
  36. Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex.
    J Neurosci. 2008 Oct 8;28(41):10434-42 PMID: 18842903
  37. Focal degeneration of astrocytes in amyotrophic lateral sclerosis.
    Cell Death Differ. 2008 Nov;15(11):1691-700 PMID: 18617894
  38. Oligodendrocyte population dynamics and the role of PDGF in vivo.
    Neuron. 1998 May;20(5):869-82 PMID: 9620692
  39. Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome.
    Nat Biotechnol. 1997 Sep;15(9):859-65 PMID: 9306400
  40. NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus.
    J Cell Biol. 2004 May 24;165(4):575-89 PMID: 15159421
  41. Mechanisms and functional implications of adult neurogenesis.
    Cell. 2008 Feb 22;132(4):645-60 PMID: 18295581
  42. Regulation of oligodendrocyte development in the vertebrate CNS.
    Prog Neurobiol. 2002 Aug;67(6):451-67 PMID: 12385864
  43. The NG2 proteoglycan: past insights and future prospects.
    J Neurocytol. 2002 Jul-Aug;31(6-7):423-35 PMID: 14501214
  44. Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination.
    Neuron Glia Biol. 2007 Aug;3(3):209-20 PMID: 18634612
  45. Postinjury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury.
    J Neurosci. 2009 May 20;29(20):6722-33 PMID: 19458241
  46. Vesicular release of glutamate from unmyelinated axons in white matter.
    Nat Neurosci. 2007 Mar;10(3):321-30 PMID: 17293857
  47. Adult glial precursor proliferation in mutant SOD1G93A mice.
    Glia. 2008 Jan 15;56(2):200-8 PMID: 18023016
  48. PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage.
    Development. 1992 Jun;115(2):535-51 PMID: 1425339
Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
Published
2010-11-18
Pages
668-81
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2989827
Subset
IM
Grants
NINDS NIH HHS · NS050274 · United States
NIMH NIH HHS · MH084020 · United States
NINDS NIH HHS · P30 NS050274-05S1 · United States
NINDS NIH HHS · NS051509 · United States
NINDS NIH HHS · P30 NS050274-059003 · United States
NINDS NIH HHS · R01 NS051509-05 · United States
NINDS NIH HHS · P30 NS050274-05 · United States
NINDS NIH HHS · R01 NS051509 · United States
NINDS NIH HHS · P30 NS050274 · United States
NIMH NIH HHS · P50 MH084020 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com